Zeaxanthin is a variety of oxygenated carotenoid widely present in nature, and is an important colorant and a component with unique physiological functions. Zeaxanthin and lutein are isomers and are the only two varieties of carotenoids present in the human retina, which have the main difference in different positions of the double bonds at their terminals, and their structural formulae are as follows.
                Zeaxanthin (Molecular Formula: C40H56O2 Molecular Weight: 568.85)        
                Lutein (Molecular Formula: C40H56O2 Molecular Weight: 568.85)        
Zeaxanthin has an important function for eye health, its mechanism of action comprises two aspects, the first is filtration of high-energy blue light in visible light, zeaxanthin can absorb near-ultraviolet blue light, the blue light has great damage to the photoreceptors and retinal cells in eyes; the second is anti-oxygenation, 11 conjugated double bonds are contained in the molecular structure of zeaxanthin, have strong oxidation resistance, can quench singlet oxygen and scavenge free radicals, and inhibit oxidative damage to the retina, crystalline lens and other tissues caused by various reasons; in addition, because the number of conjugated double bonds in the molecular structure of zeaxanthin is more than that of lutein, zeaxanthin has stronger antioxidant capacity than that of lutein, and may play a more important role in human eye health.
Zeaxanthin and lutein together constitute the only two varieties of carotenoids existing in human eyes and play an important role in human eye health. However, zeaxanthin cannot be synthesized in human body and must be taken from the outside, and the amount of zeaxanthin in human body will gradually decrease with age growth, therefore it is very necessary to supplement high-quality zeaxanthin products suitable for edible use of human through diet or dietary supplements.
In the prior art, the sources of zeaxanthin can basically be divided into three categories: full chemical synthesis method, fermentation method, and lutein isomerization method. The disadvantages of the full chemical synthesis method lie in that usually a lot of reaction steps are required, the reaction conditions are harsh with many side reactions, and the yield of the final product is low; microbes used in the fermentation method are mainly flavobacterium cells, the disadvantages of the fermentation method for production of zeaxanthin lie in that most microbes have lower fermentation unit, and the fermented product is required to be subjected to more complicated subsequent extraction and purification steps; and compared with the above two methods, zeaxanthin produced through the lutein isomerization method is regarded as a promising method, because this process involves only one reaction, and the product yield is higher and the purity is good under the premise that reaction conditions are controlled. However, many difficulties exist in the conversion process from lutein to zeaxanthin, and only one or two manufacturers can realize industrial production of zeaxanthin by using this method so far, this is because the isomerization reaction is required to be carried out in a strongly alkaline environment at higher temperature, and the stronger alkalinity is, the higher the temperature is, the better the reaction will be; but the reaction substrate lutein and the reaction product in this reaction are very unstable carotenoids, they are very unstable under a strongly alkaline and high-temperature environment, and are easy to be degraded or even carbonized. Thus, in order to pursue a high conversion rate during the reaction, a large amount of strong base would have to be used to react at a higher temperature, which will cause part of lutein and part of resulting zeaxanthin to be degraded and carbonized, therefore reaction yield is very low. In most patents previously disclosed, the production yield of zeaxanthin by way of lutein isomerization is generally about 30%, thus being far less than the requirement of industrial production.
PCT Patent Publication WO96/02594 relates to a method for producing zeaxanthin in the strongly basic solution through isomerization of lutein under the conditions of controlled temperature and pressure. But its highest yield is 24%, thereby being not suitable for industrial production.
U.S. Pat. No. 5,780,639 (Authorized Chinese Patent Publication No. CN 1082507 C) discloses a process route of producing zeaxanthin by adopting lutein as the raw material, in which the mixture of dimethyl sulphoxide or saturated alkane and/or aromatic hydrocarbon organic solvent is mainly taken as the solvent, and alkali metal hydroxide is taken as the catalyst for transposition of lutein, so as to produce zeaxanthin. This process has the disadvantages that the amount of base used is large, the reaction time is long, the product yield is low (product yield obtained by the method is less than 30% shown in repeated tests), thereby being not suitable for industrial production. Moreover, n-hexane, n-heptane, dichloromethane, methanol and other organic solvents are used during the reaction, production of food-grade or pharmaceutical-grade zeaxanthin by using these toxic solvents are clearly inappropriate.
Authorized Chinese Patent Publication No. CN 101182302 B discloses a method for preparing a composition containing zeaxanthin, which mainly adopts the scheme that isomerization of lutein is performed to prepare zeaxanthin under the catalytic action of the base catalyst and cocatalyst consisting of (formic acid, acetic acid, oxalic acid, propionic acid or sodium borohydride). This process has the disadvantages that the reaction time is long and 12-36 hr is required, the content of the final product is 30-80%, and recrystallization treatment is required to be carried out if the product with higher content is needed. Furthermore, because hexane, heptane, methanol, benzene, toluene and other organic solvents are used in the reaction process, these solvents are not suitable for use in food.
U.S. Pat. No. 7,485,738 B2 (Authorized Chinese Patent Publication No. CN 101153017 B) relates to method for preparing food-grade zeaxanthin through epimerization under the catalysis of strong organic base by using lutein as the raw material. This process has the disadvantages that the reaction time is relatively long (8-15 hr), and the yield is 60%. To sum up, the methods described in the above patents have several disadvantages: 1) some toxic organic solvents are used in the process, these solvents are difficult or impossible to be completely removed, resulting in unsuitability for human to eat the product; 2) the multi-step crystallization process is required in order to obtain high-content crystals; and 3) the reaction time is long, the temperature is high, some reaction materials and reaction products are degraded during the reaction, and the product yield is relatively low, thus being not suitable for industrial production.
Therefore, it is necessary to find a method suitable for scale industrial production of high-content zeaxanthin, less toxic organic solvents and procedures should be used in this process as much as possible, the amount of strong base should be minimized as much as possible, to shorten the reaction time and reduce the reaction temperature, but a higher reaction yield can be obtained, and the resulting product is suitable for human consumption.